Devices for intraocular drug delivery

ABSTRACT

An therapeutic agent delivery device that can allows is particularly suitable for delivery of a therapeutic agent to limited access regions, such as the posterior chamber of the eye and inner ear. Preferred devices of the invention are minimally invasive, refillable and may be easily fixed to the treatment area. Preferred delivery devices of the invention also include those that comprise a non-linear shaped body member body housing one or more substances and a delivery mechanism for the sustained delivery of the one or more substances from the non-linear shaped body member to the patient.

[0001] The present application claims the benefit of U.S. provisionalapplication 60/228,934, filed Aug. 30, 2000, which is incorporatedherein by reference in its entirety.

FIELD OF THE INVENTION

[0002] The present invention relates to a device and method forintraocular delivery of therapeutic agents. Preferred devices of theinvention include a non-linear portion that resides within a patient'seye during use that can facilitate the delivery of a therapeutic agent.

BACKGROUND

[0003] The delivery of drugs to the eye presents many challenges. Theocular absorption of systemically administered pharmacologic agents islimited by the blood ocular barrier, namely the tight junctions of theretinal pigment epithelium and vascular endothelial cells. High systemicdoses can penetrate this blood ocular barrier in relatively smallamounts, but expose the patient to the risk of systemic toxicity.Topical delivery of drugs often results in limited ocular absorption dueto the complex hydrophobic/hydrophilic properties of the cornea andsclera. Additionally, topical agents are mechanically removed by theblink mechanism such that only approximately 15% of a single drop isabsorbed. Diffusion of topically administered drugs to the posteriorchamber occurs, but often at sub-therapeutic levels. Intravitrealinjection of drugs is an effective means of delivering a drug to theposterior segment in high concentrations. However, these repeatedintraocular injections carry the risk of infection, hemorrhage andretinal detachment. Patients also find this procedure somewhat difficultto endure.

[0004] Local sustained delivery of therapeutics to the posterior chamberis critical in managing several chronic diseases of the eye. To addressthis need, several drug delivery devices have been developed forintraocular insertion into the vitreous region of the eye.

[0005] U.S. Pat. No. 4,300,557, for example, describes an intraocularimplant in the form of a silicone capsule, which can be filled with adrug to be delivered. The implant is inserted through an incision intothe vitreous region of the eye. After insertion of the implant, theincision is closed and the capsule remains in place for a period oftime. Attached to the implant is a tube that passes through the surfaceof the eye. The tube may be used for subsequent injection of a drugwhile the implant is in the eye. The implant may be removed by making asecond surgical incision into the eye and retrieving the implant. Whilein the vitreous, the device is not anchored and may move about freely.Because the overall shape of the capsule is linear, the amount of drugthat may held by the device and that may be delivered over the surfacearea of the device is limited. If the width of the capsule is increased,excessive sized incisions will be required for insertion of the device.If the length of the capsule is increased to greater than 1 cm, theimplant will pass into the central visual field of the eye, therebycausing blind spots in the patient's eye as well as increase risk ofdamage to the retinal tissue and lens capsule.

[0006] U.S. Pat. No. 5,378,475 describes a device which has beendeveloped for insertion in the vitreous region of the eye, and isdescribed in T. J. Smith et al., Sustained-Release Ganciclovir, Arch.Ophthalmol, 110, 255-258 (1992) and G. E. Sanbom, et al.,Sustained-Release Ganciclovir Therapy for Treatment of CytomegalovirusRetinitis. Use of an Intravitreal Device, Arch. Ophthalmol, 110, 188-195(1992). This device consists of an inner core of pharmacologic agentsurrounded by two coatings with different permeabilities. Drug diffusesthrough a small opening in one of these coatings achieving near-orderrelease kinetics. It is implanted in the region of the pars planathrough a 3.5-5.0 mm scleral incision. The implant must be removed andreplaced every 6 months in the operating room as the drug becomesdepleted. There is an approximately 25% complication rate from theseprocedures. The device is membrane diffusion drug delivery system thatrelies on EVA/PVA polymers to mediate release rate. Thus, many agentscannot be effectively delivered from such a system because theirpermeation rate through the rate controlling material of the system istoo small to produce a useful effect. Other agents cannot besatisfactorily delivered by diffusional devices because of a particularchemical characteristic of the agent. This includes salts, because oftheir ionic character, and unstable polar compounds that cannot beformulated into a composition suitable for storage and delivery fromsuch systems.

[0007] U.S. Pat. No. 5,098,443 describes certain specific implants thatare inserted through incisions made in the eye wall or sutured aroundthe globe of the eye. These rings may be formed from biodegradablepolymers containing microparticles of drug. Alternatively, the implantmay be in the form of a hollow flexible polymeric cocoon with the drugdisposed therewithin for slow release by osmosis. No anchoring device isdescribed.

[0008] U.S. Pat. No. 5,466,233 describes a certain tack for intraoculardrug delivery. This device has an end that is positioned in the vitreouscavity while the head remains external to the eye and abuts the scleralsurface. The tack contains a fixation portion to attempt to retainattachment within the eye. Because the overall shape of the capsule islinear, the amount of drug that may held by the device and the surfacearea through which the drug may be delivered is limited. If the width ofthe capsule is increased, excessive sized incisions will be required forinsertion of the device. If the length of the capsule is increased togreater than 1 cm, the implant will pass into the central visual fieldof the eye, thereby causing blind spots in the patient's eyes well asincrease risk of damage to the retinal tissue and lens capsule.

SUMMARY OF THE INVENTION

[0009] The present invention provides methods and devices for theintraocular delivery of substances including, for example, therapeuticagents and medicaments.

[0010] Preferred devices of the invention have a non-linear shape duringresidence within a patient's eye. Preferred designs have multiple turnsor angles, particularly substantially coil or helical configurations, atleast for those portions that reside within a patient's eye during use.

[0011] Preferred device of the invention also include those that have aquite small cross-section shape, at least with respect to areas thatreside within a patient's eye during use. Such devices can be implantedby minimally invasive surgical procedures, including without the needfor any sutures to implant or after use of the use.

[0012] An exemplary embodiment of the delivery device includes a bodymember that is non-linear in shape. In one embodiment, the device has anon-linear shape before, during and after the device is inserted intothe eye. In another embodiment, the device is fabricated of a “shapememory” material wherein the device is linear as it is inserted into theeye and wherein the device takes on a non-linear shape once it isimplanted in the eye. Preferred shape memory materials include knownmaterials such as, for example, shape memory alloys (SMA) like nitinol,shape memory polymers (SMP) like AB-polymer networks based onoligo(e-caprolactone) dimethacrylates and n-butyl acrylate.

[0013] We have found the non-linear shape of the body member provides anumber of advantages. The non-linear shape provides a built-in anchoringmechanism that prevents unwanted movement of the device and unwantedejection of the device out of the eye since the non-linear shape of thebody member requires manipulation of the device to get it out of anincision. For example, in a preferred embodiment, wherein the implant isin the shape of a coil, the device can be removed only by twisting thedevice out of the eye and, thus, is not susceptible to ejection by theeye or unwanted movement within the eye. Further, the non-linear shapegeometry of the body member provides greater surface area per length ofthe device. This is advantageous because it is desirable to limit thelength of drug delivery implants to prevent the implant from enteringthe central visual field (See FIG. 6 which follows). If the implantenters the central visual field, this will result in blind spots in thepatient's vision and will increase the risk of damage to the retinatissue and lens capsule. By forming the body member in a non-linearshape, the device of the present invention holds a greater volume ofmaterials per length of the device and it also provides a larger surfacearea per length of the device through which the material may bedelivered.

[0014] The delivery device may further include a rim or cap at itsproximal end. During use, the device is inserted into the eye through anincision until the rim or cap abuts the incision. If desired, the rim orcap may then be sutured to the eye to further stabilize and prevent thedevice from moving once it is implanted in its desired location.

[0015] In one embodiment, body member has a lumen extending along itslength for housing the substance to be delivered. Preferably, a port influid communication with the lumen is located at the proximal end of thedevice. This allows for filling and refilling of the device after thedevice has been implanted in the eye. The substance in the lumen canthen be delivered to the eye by a delivery mechanism. The lumen, in someembodiments, may further include a number of dividers to form aplurality of compartments each of which could be filled with a differentsubstance, thereby allowing for delivery of more that one substances bythe same device at the same time, if desired.

[0016] In one embodiment, the delivery mechanism comprises one or moreexit apertures located at the distal end of the body member. In anotherembodiment, the delivery mechanism comprises a plurality of openingsalong the body member. In another embodiment, the delivery mechanismcomprises the material forming the body member. For example, thematerial forming the body member may be a material that is permeable orsemi-permeable to the substance to be delivered. In another embodiment,the body member is fabricated of a synthetic biodegradable polymercontaining microparticles of the substance to be delivered. As thepolymer decomposes, the substance to be delivered is released into theeye.

[0017] Other aspects and embodiments of the invention are discussedinfra.

BRIEF DESCRIPTION OF THE DRAWINGS

[0018]FIG. 1 illustrates transcleral placement of the delivery device inaccordance with one embodiment of the present invention.

[0019]FIG. 2a illustrates the delivery device in accordance with oneembodiment of the present invention.

[0020]FIG. 2b is an enlarged view of a portion of the body member of thedelivery device shown in FIG. 2a showing the lumen.

[0021]FIG. 2c is an enlarged cross-sectional view of the body member ofthe delivery device shown in FIG. 2a.

[0022]FIG. 3a illustrates the delivery device having a deliverymechanism in accordance with one embodiment of the present invention.

[0023]FIG. 3b illustrates the delivery device having a deliverymechanism in accordance with another embodiment of the presentinvention.

[0024]FIG. 3c illustrates the delivery device having a deliverymechanism in accordance with another embodiment of the presentinvention.

[0025]FIG. 4a is an enlarged view of a portion of the body member of thedelivery device in accordance with another embodiment of the presentinvention showing a plurality of lumen.

[0026]FIG. 4b is an exploded view of the cap or rim and a portion of thebody member shown in FIG. 4a showing one arrangement of a plurality oflumen.

[0027]FIG. 4c is an exploded view of the cap or rim and a portion of thebody member shown in FIG. 4a showing another arrangement of a pluralityof lumen.

[0028]FIG. 4d illustrates another embodiment of the body membercomprising a cluster of tubes.

[0029]FIG. 5a illustrates the delivery device in accordance with anotherembodiment of the present invention showing a lumen separated into aplurality of compartments.

[0030]FIG. 5b shows the delivery device of FIG. 5a and further shows onetype of delivery mechanism in accordance with the present invention.

[0031]FIG. 6 shows a shows a cross-sectional view of an eye illustratingthe central visual field of the eye.

[0032]FIG. 7 shows a cross-sectional schematic view of an eyeillustrating one technique of pulling back of the conjunctiva to provideaccess into the eye for insertion of the delivery device of the presentinvention.

DETAILED DESCRIPTION OF THE INVENTION

[0033] As discussed above, preferred delivery devices of the inventionhave a non-linear (arcuate) shape during residence within a patient'seye. Preferred designs have multiple turns or angles. For example,preferred designs the device has at least two, three, four, five, six,seven, right, nine or ten separate deviations from a linear path. A coildesign is particularly preferred, although other multiple-angleconfigurations are also suitable such as a substantially Z-shape and thelike.

[0034] Referring now to the various figures of the drawing, wherein likereference characters refer to like parts, there is shown various viewsof a delivery device 1, in accordance with the invention.

[0035] As shown in FIGS. 1-5 c, the delivery device 1 includes anon-linear shaped body member 2 having a proximal end 4, a distal end 6.In one preferred embodiment, the body member 2 has a coil shape, asshown in FIGS. 1-5 c. However, the shape of the body member 2 is notlimited to a coil shape and other non-linear shapes may be used such as,for example, other random curled shapes, a zig-zag shape, a “J” shapeand the like. For at least some aspects of the invention, asubstantially “C” shape configuration is less preferred.

[0036] As discussed above, the non-linear shape of the body member 2provides a number of advantages. The large intravitreal surface areaprovided by the non-linear shape geometry of the body member 2 can allowfor more optimal sustained release of the substance through diffusion,enzymatic degradation, active pumping and other types of delivery. Whenimplanted in the eye, it is desirable to limit the length “L” of drugdelivery implants prevent the drug delivery implant from entering thecentral visual field “A” (See FIG. 6). If the implant enters the centralvisual field A, this will result in blind spots in the patient's visionand will increase the risk of damage to the retina tissue and lenscapsule. Thus, for example, when the implant is inserted at the parsplana, the distance from the implantation site on the pars plana to thecentral visual field is approximately 1 cm. Thus, the overall length ofthe implant is preferably less than 1 cm. By providing a body member 2that has a non-linear shape, the device of the present invention holds agreater volume of materials per length of the device without having tomake the cross section of the device and, thus, the size of theinsertion incision) larger, and it also provides a larger surface areaper length of the device through which the material may be delivered.Still further, the non-linear shape of the body member 2 provides abuilt-in anchoring system that prevents unwanted movement of the deviceand unwanted ejection of the device out of the eye since the non-linearshape of the body member requires manipulation of the device to get itout of an incision (e.g. a coil-shaped body member 2 would requiretwisting the device out of the eye, and a zig-zag shaped body member 2would require moving the device back and forth to remove the device fromthe eye).

[0037] In one preferred embodiment, the delivery device has acoil-shaped body member 2 as shown in FIGS. 1-5 c. The coil shape of thedevice provides a large intravitreal surface area through which materialcan be delivered. Further, the coil shape of the body member allows thedevice to be screwed or twisted into the eye through an incisionapproximately the same size as the outer diameter of the tube formingthe body member 2. Still further, the coil shape of the body member actsas an anchoring mechanism that holds the delivery device 1 within theeye and prevents unwanted movement of the delivery device and unwantedejection of the delivery device 1 out of the eye. Due to the coil shape,the delivery device 1 must be twisted and unscrewed out of the eye.

[0038] In general, the materials used in fabricating the body member 2are not particularly limited, provided these materials arebiocompatible. Preferably, these materials are also insoluble in thebody fluids and tissues that the device comes into contact with. It isfurther preferred that the body member 2 is fabricated of a flexiblematerial so that small movements of the delivery device will not betranslated to the retina, thereby minimizing the risk of retinaltearing, detachment and other damage. In some embodiments, as describedin further detail below, it is preferable that at least the distal end 6of body member 2 is fabricated of a rigid, non-pliable material. In someembodiments, as described in further detail below, it is preferable thatat least a portion of the material used to form the body member 2 ispermeable or semi-permeable to the substance to be delivered. In someembodiments, as set out above, it is preferable that the body member isfabricated of a material having shape memory and/or superelasticcharacteristics.

[0039] In one embodiment, the body member 2 is fabricated of anonbiodegradable polymer. Such nonbiodegradable polymers are well-knownand may include, for example, polymethylmethacrylate, a siliconeelastomer, or silicone rubber. Other suitable non-erodible,biocompatible polymers which may be used in fabricating the body member2 may include polyolefins such as polypropylene and polyethylene,homopolymers, and copolymers of vinyl acetate such as ethylene vinylacetate copolymer, polyvinylchlorides, homopolymers and copolymers ofacrylates such as polyethylmethacrylate, polyurethanes,polyvinylpyrrolidone, 2-pyrrolidone, polyacrylonitrile butadiene,polycarbonates, polyamides, fluoropolymers such aspolytetrafluoroethylene and polyvinyl fluoride, polystyrenes,homopolymers and copolymers of styrene acrylonitrile, cellulose acetate,homopolymers and copolymers of acrylonitrile butadiene styrene,polymethylpentene, polysulfones, polyesters, polyimides, natural rubber,polyisobutylene, polymethylstyrene and other similar non-erodiblebiocompatible polymers.

[0040] The body member 2 of the delivery device 1 can, in oneembodiment, have a non-linear shape prior to, during and after insertionof the device into the eye. Alternatively, the delivery device 1 can befabricated of a material having shape memory and/or superelasticcharacteristics that allows the device to be deformed and made, forexample, linear, for easier insertion into the eye and which returns toits original shape after it is inserted into the eye. In thisembodiment, the delivery device 1 has a “memory shape” that it will takeon under certain conditions. For example, the delivery device 1 may havea zig-zag or coiled memory shape. Then, when the surgeon wishes toimplant the device into the eye, the surgeon may deform the deliverydevice 1 into a linear shape for quick and easy insertion of the devicethrough an incision the size of the cross section of the linear shapeddevice. Upon insertion of the delivery device 1, the device can thentake on its zig-zag, coiled or other memory shape.

[0041] Materials having shape memory and/or superelastic characteristicsare well-known and may include any materials known in the art such as,for example, shape memory alloys (SMA) like nitinol (Ni—Ti alloy) andshape memory polymers (SMP) like AB-polymer networks based onoligo(e-caprolactone) dimethacrylates and n-butyl acrylate. Shape memoryalloys generally have at least two phases: (1) a martensite phase, whichhas a relatively low tensile strength and which is stable at relativelylow temperatures, and (2) an austenite phase, which has a relativelyhigh tensile strength and which is stable at temperatures higher thanthe martensite phase. The shape memory characteristics are imparted onthe material by heating the material to a temperature above thetemperature at which the austenite phase is stable. While the materialis heated to this temperature, the device is held in the “memory shape”,which is shape that is desired to be “remembered”. Such materials andmethods of imparting shape memory characteristics are further describedin, for example, U.S. Pat. No. 4,665,905, U.S. Pat. No. 4,925,445 andU.S. Pat. No. 6,245,100.

[0042] Preferably, the delivery device of the present invention takesadvantage of the superelastic properties of the material to extend thedevice into a linear shape. Once injected into the eye in anunconstrained form, the device will retain its memory shape.

[0043] The distal end 6 of the body member 2 may be blunt or, in someembodiments, it is pointed or has a beveled ramp-like configuration sothat the distal end 6 may be used to pierce the eye during insertion. Inone embodiment, the distal end 6 has a ramp-like angle of about 30°. Ifthe distal end 6 of the body member 2 is used to pierce the eye duringinsertion, at least the distal end 6 is fabricated of a rigid,non-pliable material suitable for piercing the eye. Such materials arewell known and may include, for example, polyimide and similarmaterials.

[0044] As shown in FIGS. 1, 2a, 3 a-c and 5 a-c, a rim or cap 8 mayfurther be located at the proximal end 4 of the body member 2 to assistin stabilizing the device 1 once implanted in the eye. Preferably, thedelivery device 1 is inserted into the eye through an incision until therim or cap 8 abuts the incision. If desired, the rim or cap 8 may thenbe sutured to the eye to further stabilize and prevent the device frommoving once it is implanted in its desired location.

[0045] The overall size and shape of the rim or cap 8 is notparticularly limited provided that irritation to the eye is limited. Forexample, while the rim or cap 8 is shown circular in shape, the rim orcap may be of any shape, for example, circular, rectangular, triangular,etc. However, to minimize irritation to the eye, the rim or cap 8preferably has rounded edges. Further, the rim or cap 8 is designed suchthat it remains outside the eye and, as such, the rim or cap 8 is sizedso that it will not pass into the eye through the opening in the eyethrough which the device is inserted. The rim or cap 8 may further bedesigned such that it can be easily sutured or otherwise secured to thesurface surrounding the opening in the eye and may, for example, containa plurality of holes (not shown) through which sutures may pass.

[0046] The materials used in fabricating the rim or cap 8 are notparticularly limited, provided these materials are biocompatible andpreferably insoluble in the body fluids and tissues that the devicecomes into contact with. Further, it is preferred that the rim or cap 8is fabricated of a material that does not cause irritation to theportion of the eye that it contacts. As such, preferred materials arepliable and may include, by way of example, various polymers including,for example, silicone elastomers and rubbers, polyolefins,polyurethanes, acrylates, polycarbonates, polyamides, polyimides,polyesters, and polysulfones.

[0047] In one embodiment, as shown in FIGS. 2a-4 c and 5 a-5 c, thenon-linear body member 2 is fabricated of a tube that is wound into acoiled shape. As shown in the Figures, the tube forming the non-linearbody member 2 is preferably cylindrical in shape, with a circularcross-section. However, the shape of the tube is not limited and, forexample, may alternatively have square, rectangular, octagonal or othercross-sectional shapes. Preferably, the tube has a lumen 10 extendingalong its length for housing the substance to be delivered. In oneembodiment, the lumen 10 is filled with the substance prior to insertingthe device into the eye. Alternatively, the lumen 10 may be filled withthe substance after the delivery device has been inserted into the eye.This may be accomplished by providing a port 12 near the proximal end 4of the body member 2 in fluid communication with the lumen 10. Thisfurther allows for refilling of the device during use, if required.

[0048] In one embodiment, the port 12 is preferably designed such thatthe needle of a syringe, or similar injection mechanism, may be insertedinto the port 12 and the substance injected by the syringe or-injectionmechanism. Thus, the substance travels through the port 12 and into thelumen 10. The port 12 preferably forms a snug seal about the needle ofthe syringe or injection mechanism to prevent leakage of the substanceout of the port 12 around the syringe needle or injection mechanism andto provide sterile injection of agent into the lumen 10. If desired,fittings or collars (not shown), through which a syringe needle orinjection mechanism may be inserted and which form a snug seal about thesyringe needle or injection mechanism, may be mounted on the port 12.Upon injection of the substance into the delivery device, the needle ofthe syringe or the injection mechanism is removed from the port 12 andthe port 12 sealed. This may be accomplished by providing a removablecover (not shown) on the port 12 that may be removed for injection ofthe substance and replaced when the substance has been injected. In apreferred embodiment, the port 12 is fabricated of an injectableself-sealing material through which the needle or injection mechanismmay be inserted and which seals off automatically when the needle orinjection mechanism is removed. Such materials are known and include,for example, silicone rubber, silicone elastomers and polyolefin.

[0049] Once the device is implanted in the desired location and thesubstance is housed within the lumen 10, the substance can then bedelivered to the eye by a delivery mechanism.

[0050] In one embodiment, as shown in FIG. 3a, the delivery mechanismcomprises an exit aperture 16 located at the distal end 6 of the bodymember 2. Alternatively, as shown in FIG. 3b, a plurality of exitapertures 16 a located at the distal end 6 of the body member 2 may formthe delivery mechanism. The number and size of the one or more exitapertures 16 may vary depending on the desired rate of delivery of theagent and may be readily determined by one of skill in the art. The oneor more exit apertures 16 are designed such that the substance is slowlydiffused rather than expelled as a fluid stream, which may damage thedelicate tissues of the eye. For example, in one embodiment, this may beachieved by, for example, placing a covering or lining (not shown) overthe distal exit aperture 16, wherein the covering or lining has aparticular porosity to the agent or wherein the covering or lining isfabricated of a diffusion or rate-limiting membrane, matrix material orsimilar material.

[0051] In another embodiment, for example, as shown in FIG. 3c, thedelivery mechanism comprises a plurality of openings 18 along the bodymember 2. The number and size of the one or more openings 18 may varydepending on the desired rate of delivery of the agent and may bereadily determined by one of skill in the art. Further, the location ofthe plurality of openings 18 may be situated so as to deliver thesubstance at a particular location once the device is implanted in theeye. The plurality of openings 18 are designed such that the substanceis slowly diffused rather than expelled as a fluid stream, which maydamage the delicate tissues of the eye. In this embodiment, an exitaperture 16 at the distal end 6 of the body member 2 as described abovemay also be included.

[0052] In another embodiment, the delivery mechanism comprises thematerial forming the body member 2. For example, the material formingthe body member 2 may be a material that is permeable or semi-permeableto the substance to be delivered. Such materials may vary depending onthe particular application and the substance to be delivered and may bereadily determined by one of skill in the art. By way of example, somesuitable permeable materials may include polycarbonates, polyolefins,polyurethanes, copolymers of acrylonitrile, copolymers of polyvinylchloride, polyamides, polysulphones, polystyrenes, polyvinyl fluorides,polyvinyl alcohols, polyvinyl esters, polyvinyl butyrate, polyvinylacetate, polyvinylidene chlorides, polyvinylidene fluorides, polyimides,polyisoprene, polyisobutylene, polybutadiene, polyethylene, polyethers,polytetrafluoroethylene, polychloroethers, polymethylmethacrylate,polybutylmethacrylate, polyvinyl acetate, nylons, cellulose, gelatin,silicone rubbers and porous rubbers.

[0053] The particular material used to fabricate the body member 2 maybe chosen to provide a particular rate of delivery of the substance,which may be readily determined by one of skill in the art. Further, therate of delivery of the substance may also be increased or decreased byvarying the percentage of the body member 2 formed of the materialpermeable to the agent. Thus, for example, to provide a slower rate ofdelivery, the body member 2 may be fabricated of 50% or less permeablematerial. For example, the body member 2 may be fabricated of 1%, 5%,10%, 20%, 30%, 40% or 50% of permeable material. For a faster rate ofdelivery, the body member 2 may be fabricated of greater than 50% ofpermeable material. For example, the body member 2 may be fabricated of51%, 55%, 60%, 70%, 80%, 90% or 100% of permeable material. When one ormore portions of the body member 2, rather than the whole body member 2,is fabricated of a permeable or semi-permeable material, the location ofthe permeable or semi-permeable material may be situated so as todeliver the substance at a particular location once the device isimplanted in the eye.

[0054] In another embodiment, the body member 2 is fabricated of asynthetic biodegradable polymer containing microparticles of thesubstance to be delivered. Thus, in this embodiment, as the polymerdecomposes, the substance to be delivered is released into the eye.Release time is a function of the polymer and the shape and size of thebody. member 2 and may be readily determined by one of ordinary skill inthe art. Such biodegradable polymers may vary depending on theparticular application and may be readily determined by one of skill inthe art. By way of example, some suitable biodegradable polymers mayinclude polyesters of molecular weight from about 4,000 to about100,000, homopolymers and copolymers of polylactic acid and polyglycolicacid, polycaprolactone, homopolymers and copolymers of polyanhydridessuch as terephthalic acid anhydride, bis(p-anhydride) andpoly(p-carboxyphenoxy) alkyl, homopolymers and copolymers ofdicarboxylic acids such as sebacic, adipic, oxalic, phthalic and maleicacid, polymeric fatty acid dimer compounds such as polydodecanedioicacid polyorthoesters, poly(alkyl-2-cyanoacrylate) such aspoly(hexyl-2-cyanoacrylate), collagen (gelatin), polyacetals,divinyloxyalkylenes, polydihydropyrans, polyphosphazenes, homopolymersand copolymers of amino acids such as copolymers of leucine and methylglutamate, polydioxinones, polyalkylcyano acetates, polysaccarides andtheir derivatives such as dextran and cyclodextran, cellulose andhydroxymethyl cellulose.

[0055] In another embodiment, rather than a single lumen 10, thenon-linear body member 2 includes a plurality of lumens 10 a capable ofhousing and delivering a plurality of substances. Thus, for example,each lumen 10 a may be in fluid communication with plurality of ports 12a. These ports 12 a are similar to the single port 12 described above.(e.g. the ports 12 a may include a cover that may be removed forinjection of the substance and replaced when the substance has beeninjected, or the ports 12 a may be fabricated of an injectableself-sealing material) If desired, the lumens 10 a and ports 12 a may bearranged such that each lumen 10 a may be filled with a differentsubstance through the corresponding ports 12 a. Thus, the single devicemay be used to deliver more than one substance if desired.

[0056] In one embodiment, the plurality of lumens 10 a are situated in aring about the outer circumference of the body member 2 as shown in FIG.4b. The substance(s) may be injected into the lumens 10 a for deliverythrough a delivery mechanism, which may be any of the deliverymechanisms described above or a combination of the delivery mechanismsdescribed above.

[0057] In another embodiment, a plurality of lumen 10 a are clusteredwithin the body member 2 as shown in FIG. 4c. The substance(s) may beinjected into the lumens 10 a for delivery through a delivery mechanism.In this embodiment, the inner lumens 10 a preferably deliver theirhoused substances through one or more apertures 16, 16 a located nearthe distal end 6 of the body member 2, while the outer lumens 10 alocated at the outer circumference of the body member 2 may delivertheir housed substances through one or more apertures 16, 16 a locatednear the distal end 6 of the body member 2, a plurality of openings 18along the body member 2, and/or through the material forming the bodymember 2 as described above.

[0058] In yet another embodiment, the non-linear body member 2 is formedof a plurality of tubes 20 clustered-and wound into a coil shape asshown in FIG. 4d. In this embodiment, the substance(s) to be deliveredis/are inserted into and housed within the plurality of hollow tubes 20.The plurality of tubes 20 may contain different substances or the samesubstance as desired. The substances are then delivered by one or moreof the delivery mechanisms set out above. For example, in oneembodiment, one or more of the tubes 20 may have one or more exitapertures 22 at their distal ends through which the substance(s) can bedelivered. One or more tubes 20 may also have a plurality of openings 24along their lengths through which the substance(s) can be delivered.Still further, one or more tubes 20 can be fabricated of a materialpermeable or semi-permeable to the substance contained within the tubes20. Thus, it is possible for each tube 20 to have one or more of thevarious types of delivery mechanisms and, also, it is possible to fordifferent tubes to have different types of delivery mechanisms. In thisway, each tube 20 can be designed to provide the optimal type ofdelivery based on the substance to be delivered, the location ofdelivery and the desired rate of delivery.

[0059] In another embodiment, a plurality of substances may be deliveredby a single device by providing a body member 2 with a lumen 10 havingimpermeable dividers 25 located along the length of the lumen 10 asshown for example, in FIG. 5a. Thus, the lumen 10 would contain aplurality of compartments 26, each of which could be filled with adifferent substance. These compartments 26 could be filled prior toinsertion through an injection port 32 located, for example, in the sideof each compartment 16 as shown in FIG. 5b. In another embodiment, thedevice may be filled after it is implanted by providing a plurality ofconduits 30 each in fluid communication with a corresponding compartment25. These conduits 30 may be located within the wall of the body member2, along the circumference of the body member 2, for example, as shownin FIG. 5c. The substances could then be injected through a plurality ofports 34 a, 34 b, 34 c, 34 d, 34 e each in fluid communication with acorresponding conduit 30. Thus, a substance could be injected into thefirst compartment 26 a just below the rim or cap 8 by a port 34 a in thecenter of the rim or cap 8, which delivers the substance directly intothe first compartment 26 a. A substance injected into the second port 36b, would flow through conduit 30 and would flow through an aperture inthe wall of the body member 2 into second compartment 26 b, and so on.

[0060] The substance injected into each of the compartments 26 a, 26 b,26 c, 26 d, 26 e, is then delivered to the eye by a delivery mechanism,which may be one or more of the delivery mechanisms described above. Forexample, substance in compartment 26 a may be delivered through one ormore apertures 36 in the walls of the compartment 26 a. Compartment 26 bcould be fabricated of a material that is permeable or semi-permeable tothe substance in the compartment 26 b such that substance in compartment26 b may be delivered by diffusion through the walls of the compartment.Such materials are set out above and may be readily determined by thosein skill in the art depending on-the substance in the compartment to bedelivered and the desired rate of delivery of the substance. Substancein compartment 26 e, located at the end of the non-linear body member 2could be delivered by an exit port (not shown) located at the distal endof the compartment 26 e and, also, could be delivered by a plurality ofapertures (not shown) in the walls of the compartment 26 e. In this way,each compartment may be designed for optimal delivery the particularsubstance housed within the compartment.

[0061] In another embodiment, each compartment 26 a, 26 b, 26 c, 26 d,26 e is designed for selective “opening” or activation by a laser (viaheat or photodisruption). For example, a laser could be used to createapertures in the walls of the desired compartment 26 a, 26 b, 26 c, 26 dor 26 e when the particular substance is to be delivered. As such,release of each substance could be controlled upon demand by aphysician.

[0062] In yet another embodiment, a pump-driven (e.g. Spring,gas-driven, nitinol, piezoelectric, osmotic) system (not shown)including is coupled to the device, allowing for more sustaineddelivery. In this embodiment, the one or more lumens 10, 10 a can berefilled by injection into the lumen(s) 10, 10 a themselves or throughan external conduit. For example, a separate pump device and reservoirhousing one or more substances (not shown) could be located within theeye or remotely (i.e. behind the ear subcutaneously). If the pump andreservoir are located behind the ear, a conduit between the pump and thedelivery device within the eye could run subcutaneously into the orbit,subconjunctively and through the sclera into the posterior chamber. Theconduit must have sufficient slack to allow for ocular movements withoutdisplacing the conduit.

[0063] For added structural support, the delivery device may furtherinclude a nonbiodegradable backbone (not shown) located along thenon-linear body member 2. For example, in one embodiment, one or morethin, wire-like members fabricated of a nonbiodegradable material, maybe located within the walls of the body member 2 or, for example, in thecenter of the cluster of tubes 20 shown in FIG. 4d. Suchnonbiodegradable materials are well-known and may be readily determinedby one of skill in the art. By way of example, some suitablenonbiodegradable polymers may include, for example,polymethylmethacrylate, a silicone elastomer, or silicone rubber. Othersuitable non-erodible, biocompatible polymers which may be used infabricating the body member 2 may include polyolefins such aspolypropylene and polyethylene, homopolymers, and copolymers of vinylacetate such as ethylene vinyl acetate copolymer, polyvinylchlorides,homopolymers and copolymers of acrylates such as polyethylmethacrylate,polyurethanes, polyvinylpyrrolidone, 2-pyrrolidone, polyacrylonitrilebutadiene, polycarbonates, polyamides, fluoropolymers such aspolytetrafluoroethylene and polyvinyl fluoride, polystyrenes,homopolymers and copolymers of styrene acrylonitrile, cellulose acetate,homopolymers and copolymers of acrylonitrile butadiene styrene,polymethylpentene, polysulfones, polyesters, polyimides, natural rubber,polyisobutylene, polymethylstyrene and other similar non-erodiblebiocompatible polymers.

[0064] In another embodiment, the delivery device 1 includes backbone(not shown) fabricated of a shape memory material described above. Inthis embodiment, for example, the body member 2 may be fabricated of anyof the materials described above. In one embodiment, for example, thebody member 2 is fabricated of a flexible material and a shape memorybackbone located within the wall of the body member 2 or, for example,in the center of a cluster of tubes 20 shown in FIG. 4d. Thus, thebackbone, along with the body portion of the device, is first deformedto a shape that makes it easier to insert into the eye, such as a linearshape. The backbone will hold the device in this deformed shape. Afterthe device is inserted into the eye, the backbone, along with the bodyportion of the device, will then return to the remembered shape.

[0065] The dimensions of the delivery device will depend on the intendedapplication of the device, and will be readily apparent to those havingordinary skill in the art. By way of example, when the delivery deviceis used to deliver substances to the posterior chamber of the eye, thedevice is preferably designed for insertion through a small incisionthat requires few of no sutures for scleral closure at the conclusion ofthe procedure. As such, the device is preferably inserted through anincision that is no more than about 1 mm in cross-section, e.g. rangingfrom about 0.25 mm to about 1 mm in diameter, more preferably less than0.5 mm in diameter. As such, the cross-section of the tube forming thebody member 2, or the cluster of tubes 20 as shown in FIG. 4d, ispreferably no more than about 1 mm, e.g. preferably ranging from about0.25 mm to about 1 mm in diameter, and, more preferably, is no greaterthan 0.5 mm. If the tube forming the body member 2 is not cylindrical,the largest dimension of the cross section can be used to approximatethe diameter for this purpose. When used to deliver agents to theposterior chamber of the eye, the body member 2 preferably has a lengthfrom its proximal end 4 to its distal end 6 that is less than about 1.5cm, e.g. ranges from about 0.5 cm to about 1.5 cm such that when the ribor cap 8 abuts the outer surface of the eye, the delivery mechanism ispositioned near the posterior chamber of the eye.

[0066] The use of the delivery device of the present invention can befurther understood from the following discussion relating to a methodfor treating chronic diseases of the eye by sustained release oftherapeutic agent to the eye and with reference to FIGS. 1-6.

[0067] The delivery device is generally used by the following procedure:the delivery device is prepared, either empty or housing the substanceto be delivered.

[0068] In one embodiment, an incision is made to provide access to thetreatment site. For example, when used to deliver therapeutic agent tothe posterior chamber of the eye, a sclerotomy is created for insertionof the delivery device. Conventional techniques may be used for thecreation of the sclerotomy. Such techniques require the dissection ofthe conjunctiva 44 and the creation of pars plana scleral incisionsthrough the sclera 46. As shown in FIG. 6, the dissection of theconjunctiva 44 typically involves pulling back the conjunctiva 44 aboutthe eye 42 so as to expose large areas of the sclera 46 and the clippingor securing of the conjunctiva 44 in that pulled back state (normalposition of conjunctiva shown in phantom). In other words, the sclera 46is not exposed only in the areas where the pars plana scleral incisionsare to be made. Surgical instruments used in the procedure are thenpassed through these incisions. Thus, the incisions created for theprocedure must be made large enough to accommodate the instrumentsrequired for the procedure. Alternatively, during this procedure, ratherthan making an incision through which the device is inserted, the distalend 6 may be pointed or beveled and used to create the incision.

[0069] Alternatively, the creation of the sclerotomy may be accomplishedby use of an alignment device and method, such as that described in U.S.Ser. No. 09/523,767, the teachings of which are incorporated herein byreference, that enables sutureless surgical methods and devicestherefore. In particular, such methods and devices do not require theuse of sutures to seal the openings through which instruments areinserted. The alignment devices are inserted through the conjunctiva andsclera to form one or more entry apertures. Preferably, the alignmentdevices are metal or polyimide cannulas through which the surgicalinstruments used in the procedure are inserted into the eye.

[0070] The body member 2 is then inserted into the eye. For example, inembodiments wherein the body member 2 has a coiled shape, the bodymember 2 is inserted into the eye by screwing or twisting the bodymember 2 into eye until the rim or cap 8 abuts the outer surface of theeye. In embodiments wherein the body member 2 or a backbone of the bodymember is fabricated of a shape memory material, the shape memorymaterial is first cooled to a temperature at which the martensite phaseis stable and the device is deformed, for example, into a linear shape.The device is then inserted into the eye. To return the device to itsmemory shape, the device is left unrestrained and is simply heated to atemperature above the martensite phase temperature. For example, theshape memory material may be heated by a laser to return the device to atemperature above the martensite phase temperature. The shape memorymaterial may also be selected such that the martensite phase temperatureis below body temperature so that the material is simply cooled to belowbody temperature, deformed to a linear shape and inserted into the eye.Then, as the material warms up within the eye to body temperature, thedevice returns to its remembered shape.

[0071] After the device is inserted into the eye, the rim or cap 8 maythen be sutured or otherwise secured to the sclera to hold the deliverydevice in place. If a cover is used to close the port(s) 12, 12 a it isremoved at this time, and, if used, a collar for providing a snug fitabout the syringe or other injection mechanism is mounted on the port(s)12, 12 a. The syringe or other injection mechanism is then connected tothe port(s) 12, 12 a for injection of the one ore more substances intothe delivery device. If the port(s) 12, 12 a are composed of aninjectable self-sealing material through which the needle of a syringeor other injection mechanism may be inserted and which seals offautomatically when the needle other injection mechanism is removed, theneedle or other injection mechanism is simply inserted through the portand the substance injected. Following injection, the conjunctiva may beadjusted to cover the rim or cap 8 of the device.

[0072] When the device is used to deliver agents to the eye for thetreatment of a variety of ocular conditions such as, for example,retinal detachment, occlusions, proliferative retinopathy, diabeticretinopathy, inflammations such as uveitis, choroiditis and retinitis,degenerative disease, vascular diseases and various tumors includingneoplasms, some substances suitable for delivery to the eye may include,for example, antibiotics such as tetracycline, chlortetracycline,bacitracin, neomycin, polymyxin, gramicidin, cephalexin,oxytetracycline, chloramphenicol, rifampicin, ciprofloxacin, tobramycin,gentamycin, and erythromycin and penicillin; antifungals such asamphotericin B and miconazole; antibacterials such as sulfonamides,sulfadiazine, sulfacetamide, sulfamethizole and sulfisoxazole,nitrofurazone and sodium propionate; antivirals, such as idoxuridinetrifluorotymidine, acyclovir, ganciclovir and interferon; antibacterialagents such as nitrofurazone and sodium propionate; antiallergenics suchas sodium cromoglycate, antazoline, methapyriline, chlorpheniramine,cetirizine, pyrilamine and prophenpyridamine; anti-inflammatories suchas hydrocortisone, hydrocortisone acetate, dexamethasone 21-phosphate,fluocinolone, medrysone, methylprednisolone, prednisolone 21-phosphate,prednisolone acetate; fluoromethalone, betamethasone and triamcinolone;non-steroidal anti-inflammatories such as salicylate, indomethacin,ibuprofen, diclofenac, flurbiprofen and piroxicam; decongestants such asphenylephrine, naphazoline and tetrahydrozoline; decongestants such asphenylephrine, naphazo line, and tetrahydrazoline; miotics andanti-cholinesterase such as pilocarpine, salicylate, carbachol,acetylcholine chloride, physostigmine, eserine, diisopropylfluorophosphate, phospholine iodine, and demecarium bromide; mydriaticssuch as atropine sulfate, cyclopentolate, homatropine, scopolamine,tropicamide, eucatropine, and hydroxyamphetamine; sympathomimetics suchas epinephrine; antineoplastics such as carmustine, cisplatin andfluorouracil; immunological drugs such as vaccines and immunestimulants; hormonal agents such as estrogens, estradiol,progestational, progesterone, insulin, calcitonin, parathyroid hormoneand peptide and vasopressin hypothalamus releasing factor; betaadrenergic blockers such as timolol maleate, levobunolol HCl andbetaxolol HCl; growth factors such as epidermal growth factor,fibroblast growth factor, platelet derived growth factor, transforminggrowth factor beta, somatotropin and fibronectin; carbonic anhydraseinhibitors such as dichlorophenamide, acetazolamide and methazolamnide;inhibitors of angiogenesis such as angiostatin, anecortave acetate,thrombospondin, and anti-VEGF antibody; and other therapeutic agentssuch as prostaglandins, antiprostaglandins and prostaglandin precursors.

[0073] In some applications, additives may further be included in thesubstance and, for example, some suitable additives may include water,saline, dextrose, carriers, preservatives, stabilizing agents, wettingagents, emulsifying agents or other similar materials.

[0074] Once the therapeutic agent had been delivered to the treatmentarea, the delivery device may be refilled for further delivery orremoved if the required dose of agent has been delivered for treatmentof the condition.

[0075] The invention is not be limited to ocular applications, and isparticularly useful in other limited access regions such as the innerear.

[0076] The present invention also includes kits that comprise one ormore devices of the invention, preferably packaged in sterile condition.Kits of the invention also may include, for example, one or more bodymembers 2, means for suturing or securing the device to the sclera, etc.for use with the device, preferably packaged in sterile condition,and/or written instructions for use of the device and other componentsof the kit.

[0077] All documents mentioned herein are incorporated by referenceherein in their entirety.

[0078] The foregoing description of the invention is merely illustrativethereof, and it is understood that variations and modifications can beeffected without departing from the scope or spirit of the invention asset forth in the following claims.

What is claimed is:
 1. An implantable delivery device for intraoculardelivery comprising: a non-linear shaped body member having a proximalend and a distal end; a lumen extending through the coil shaped bodymember for housing a substance to be delivered; a delivery mechanism fordelivery of the substance, whereby the non-linear shape of the bodymember provides an increased surface area per length of the devicethrough which drug delivery occurs.
 2. The delivery device of claim 1wherein the member has multiple angles.
 3. The delivery device of claim1 or 2 wherein the body member is coil-shaped.
 4. The delivery device ofany one of claims 1 through 3 further comprising a port near theproximal end of the non-linear shaped body member for introducing thesubstance to the lumen.
 5. The delivery device of any one of claims 1through 4 further comprising a rim or cap at the distal end of thedevice for stabilizing the device at a desired delivery area wherein thenon-linear shaped body member in inserted into the eye until the rim orcap abuts the outer surface of the eye.
 6. The delivery device of claim5, wherein the rim or cap includes one ore more holes for suturing thedevice to the eye.
 7. The delivery device of claim 5 or 6 wherein therim or cap is fabricated of a pliable material.
 8. The delivery deviceof any one of claims 5 through 7 wherein the rim or cap is fabricated ofa material selected from, silicone elastomers and rubbers, polyolefins,polyurethanes, acrylates, polycarbonates, polyamides, polyimides,polyesters, and polysulfones.
 9. The delivery device of any one ofclaims 1 through 8 wherein the device comprises a delivery mechanismcomprises at least one exit aperture located at the distal end of thenon-linear shaped body member.
 10. The delivery device of claim 9wherein the size and/or number of the at least one exit aperturecontrols the rate of delivery of the substance.
 11. The delivery deviceof claim 9 or 10 further comprising a mechanism for controlling the rateof delivery of the substance through the at least one exit aperture. 12.The delivery device of any one of claims 9 through 11 wherein themechanism for controlling the rate of delivery of substance comprises aporous lining, a matrix material, a diffusion-limiting material orrate-limiting membrane that covers the at least one exit aperture. 13.The delivery device of any one of claims 1 through 8 wherein the devicecomprises a delivery mechanism comprises a plurality of openings alongthe coil shaped body member.
 14. The delivery device of claim 13 whereinthe size and/or number of the at least one openings controls the rate ofdelivery of the substance.
 15. The delivery device of any one of claims1 through 8 wherein the device comprises a delivery mechanism comprisesa permeable or semi-permeable material forming at least a portion of thenon-linear shaped body member.
 16. The delivery device of claim 15wherein the percentage of the non-linear shaped body member fabricatedof a permeable or semi-permeable material controls the rate of deliveryof the substance.
 17. The delivery device of claim 15 wherein thepermeability of the material to the substance controls the rate ofdelivery of the substance.
 18. The delivery device of claim 15 whereinthe permeable or semi-permeable material is selected frompolycarbonates, polyolefins, polyurethanes, copolymers of acrylonitrile,copolymers of polyvinyl chloride, polyamides, polysulphones,polystyrenes, polyvinyl fluorides, polyvinyl alcohols, polyvinyl esters,polyvinyl butyrate, polyvinyl acetate, polyvinylidene chlorides,polyvinylidene fluorides, polyimides, polyisoprene, polyisobutylene,polybutadiene, polyethylene, polyethers, polytetrafluoroethylene,polychloroethers, polymethylmethacrylate, polybutylmethacrylate,polyvinyl acetate, nylons, cellulose, gelatin, silicone rubbers andporous rubbers.
 19. The delivery device of any one of claims 1 through 8wherein the device comprises a delivery mechanism that comprises abiodegradable polymeric material forming at least a portion of thenon-linear shaped body member.
 20. The delivery device of claim 19wherein the biodegradable polymeric material contains microparticles ofthe therapeutic agent to be delivered.
 21. The delivery device of anyone of claims 1 through 21 wherein the distal end of the body member isadapted for piercing the eye during insertion into the eye.
 22. Thedelivery device of claim 22 wherein the body member distal end ispointed or beveled.
 23. The delivery device of any one of claims 1through 22 wherein the cross-sectional shape of the non-linear shapedbody member is circular.
 24. The delivery device of any one of claims 1through 23 wherein the device may be inserted through an incisionrequiring few or no sutures for closure.
 25. The delivery device ofclaim 24 wherein the largest cross-section dimension of the member isfrom about 0.25 mm to about 1 mm.
 26. The delivery device of claim 24wherein the largest cross-section dimension of the body member is fromabout 0.25 mm to about 0.5 mm.
 27. The delivery device of any one ofclaims 1 through 26 wherein the port near the proximal end of the bodymember forms a seal about the needle of a syringe or injection mechanismused to introduce the substance to the lumen.
 28. The delivery device ofany one of claims 1 through 26 further comprising a collar mounted aboutthe distal end of the body member through which the needle of a syringeor injection mechanism may be inserted and which forms a seal about theneedle of a syringe or injection mechanism.
 29. The delivery device ofany one of claims 1 through 28 wherein the port near the proximal end ofthe body member is fabricated of an injectable self-sealing material.30. The delivery device of claim 29 wherein the injectable self-sealingmaterial is selected from silicone rubber, silicone elastomers andpolyolefin.
 31. The delivery device of any one of claims 1 through 30wherein the body member is fabricated of a flexible material thatprevents small movements of the delivery device from being translated tothe retina.
 32. An implantable delivery device for intraocular deliverycomprising a coil shaped body member having a proximal end and a distalend.
 33. The delivery device of claim 32 wherein at least a portion ofthe coil shaped body member fabricated of a biodegradable polymericmaterial containing microparticles of the substance to be delivered,whereby as the polymeric material decomposes, the substance isdelivered.
 34. An implantable delivery device for intraocular deliverycomprising: a non-linear shaped body member having a proximal end and adistal end; and a plurality of lumens extending through the body memberfor housing at least one substance to be delivered.
 35. The deliverydevice of claim 34 wherein the device further comprises a deliverymechanism for delivery of the substance.
 36. The delivery device ofclaim 34 or 35 wherein the body member is coil-shaped.
 37. The deliverydevice of any one of claims 34 through 36 further comprising a pluralityof ports, each in fluid communication with a corresponding lumen forintroducing the substance to each of the lumens.
 38. An ocular drugdelivery device comprising: a non-linear shaped body member that has ashape other than a substantially C-configuration.
 39. The deliverydevice of any one of claims 1 through 38 wherein the non-linear shapedbody member is fabricated of a cluster of hollow tubes formed into anon-linear shape, each tube having a lumen for housing at least onesubstance to be delivered.
 40. The delivery device of claim 39 whereinthe lumen is divided into a plurality of compartments along the lengthof the lumen by at least one impermeable divider.
 41. The deliverydevice of claim 40 wherein a different substance is inserted and housedwithin each of the plurality of compartments.
 42. The delivery device ofclaim 40 or 41 wherein the plurality of compartments may each beselectively opened by a laser for delivery of the substance within eachcompartment.
 43. The delivery device of any one of claims 1 through 42further including a backbone extending through at least a portion of thenon-linear shaped body member for added structural support of thenon-linear shaped body member.
 44. The delivery device of any one ofclaims 32 through 43 wherein the device may be inserted through anincision requiring few or no sutures for closure.
 45. The deliverydevice of claim 44 wherein the largest cross-section dimension of thebody member is from about 0.25 mm to about 1 mm.
 46. The delivery deviceof claim 44 wherein the largest cross-section dimension of the bodymember ranges from about 0.25 mm to about 0.5 mm.
 47. The deliverydevice of any one of claims 1 through 46 wherein at least a portion ofthe body member is fabricated of a shape memory material, whereby thebody member may be deformed into a shape that allows easier insertion ofthe device into the eye and whereby the device returns to a non-linearremembered shape after insertion in the eye.
 48. The delivery device ofany one of claims 1 through 47 wherein the body member has a backbonefabricated of a shape memory material, whereby the body member may bedeformed into a shape that allows easier insertion of the device intothe eye and whereby the device returns to a non-linear remembered shapeafter insertion in the eye.
 49. An implantable delivery device forintraocular delivery comprising: a body member having a proximal end anda distal end; at least a portion of the body member fabricated of ashape memory material; whereby the remembered shape of the body memberis non-linear, and whereby the body member may be deformed into a shapethat allows easier insertion of the device into the eye and whereby thedevice returns to its non-linear remembered shape after insertion in theeye.
 50. The delivery device of any one of claims claim 47 through 49wherein the remembered shape of the body member is a coil shape.
 51. Thedelivery device of any one of claims 47 through 50, wherein the shapememory material is selected from shape memory alloys and shape memorypolymers.
 52. A device for drug delivery comprising: a body memberhaving a maximum cross-section dimension of from about 0.25 mm to about1 mm.
 53. The delivery device of claim 53 wherein the maximumcross-section dimension of the body member is from about 0.25 mm toabout 0.5 mm.
 54. The delivery device of claim 52 wherein the maximumcross-section dimension of the body member is from about 0.25 mm toabout 0.4 mm.
 55. The delivery device of any one of claims 52 through 54wherein the device is implantable with a human eye.
 56. A medical devicekit, comprising one or more of the delivery devices of any one of claims1 through
 55. 57. The kit of claim 56 wherein the one or more deliverydevices are packaged in sterile condition.
 58. A method for delivery ofa therapeutic agent to a patient's eye comprising: (a) providing adelivery device of any one of claims 1 through 54 wherein the devicecontains a therapeutic agent; and (b) inserting the device into apatient's eye.
 59. The method of claim 58 wherein after insertion of thedevice, the therapeutic agent enters the patient's eye.
 60. The methodof claim 58 or 59 wherein the therapeutic agent is administeredintraocularly to the patient.
 61. A method for delivery of a substanceintraocularly, comprising: (a) providing a sustained release deliverydevice comprising: a non-linear shaped body member having a proximal endand a distal end; a lumen extending through the non-linear shaped bodymember for housing a substance to be delivered; a delivery mechanism fordelivery of the substance; (b) making an incision in a patient's eye toaccess a treatment area; (c) inserting the delivery device into thetreatment area through the incision distal end first; (d) allowing thesubstance to travel out of the lumen and to the eye through the deliverymechanism; (e) removing the delivery device from the treatment area. 62.A method for delivery of a substance intraocularly, comprising: (a)providing a sustained release delivery device comprising: a non-linearshaped body member having a proximal end and a distal end; a lumenextending through the non-linear shaped body member for housing asubstance to be delivered; a delivery mechanism for delivery of thesubstance; a port at the distal end of the non-linear shaped body memberfor injection of the substance into the lumen; (b) making an incision ina patient's eye to access the treatment area; (c) inserting the deliverydevice into the treatment area through the incision distal end firstsuch that the port remains outside the incision; (d) using an injectionmechanism to inject the substance into the lumen through the port; (e)removing the injection mechanism from the port and closing off the port;(f) allowing the substance to travel out of the lumen and to the patientthrough the a delivery mechanism; (g) optionally repeating steps (d)through (f) one or more times; and (h) removing the delivery device fromthe treatment area.
 63. The method of claim 58 through 62 wherein thebody member is coil-shaped and wherein the step of inserting thedelivery device into the treatment area through the incision distal endfirst comprises twisting the coil-shaped body member in through theincision.
 64. A method for delivery of a therapeutic agent comprisinginserting a delivery device of any one of claims 1 through 54 into apatient ocular treatment area and allowing the delivery mechanism todeliver the substance to a treatment area at a desired rate.
 65. Amethod for the treatment of ocular conditions in patients comprisingutilizing the delivery device of any one of claims 1 through 54 todeliver one or more therapeutic agents to the eye of the patient. 66.The method of any one of claims 58 through 64 wherein at least a portionof the body member is fabricated of a shape memory material, the methodfurther comprising the step of, prior to insertion of the device intothe eye, deforming the body member into a shape that allows easierinsertion of the device into the eye, whereby after the device isinserted into the eye the device returns to a non-linear rememberedshape.
 67. The method of claim 65 or 66 wherein the member has asubstantially coil configuration.